Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan.
School of Psychology, Chung Shan Medical University, Taichung, Taiwan.
Cancer Med. 2023 Jan;12(1):747-759. doi: 10.1002/cam4.4920. Epub 2022 Jun 6.
ADH1B rs1229984 and ALDH2 rs671 are the specifically prevalent functional variants in the East Asians. These variants, which result in a dramatic change in enzyme activity, are highly associated with alcohol-related disorders and cancer. Previous studies focusing on the additive and synergic effects of the variants are few and inconsistent. The aim of the research was to evaluate the associations of ADH1B rs1229984 and ALDH2 rs671 with the risks of alcohol-related disorder and cancer.
This cohort study enrolled 42,665 participants from the Taiwan Precision Medicine Initiative database, including 19,522 and 20,534, ADH1B and ALDH2 carriers, respectively. The associations between the two variants and cancer risk were analyzed by univariable and multivariable logistic regression.
Compared with the noncarriers, the ADH1B rs1229984 variant had a stronger effect on alcohol-related disorders and was related to an increased risk of alcohol-related cancers. The CC genotype of ADH1B rs1229984 was significantly associated with cancer of the larynx, pharynx, and nasal cavities [odds ratio (OR) = 1.56, p = 0.0009], cancer of the pancreas (OR = 1.66, p = 0.018), and cancer of the esophagus (OR = 4.10, p < 0.001). Participants who carried the rs1229984 TC/CC and rs671 GG genotypes were at higher risk of esophageal cancer (OR = 3.02, p < 0.001). The risk of esophageal cancer was increased by 381% (OR = 4.81, p < 0.001) in those carrying the rs1229984 TC/CC and rs671 GA/AA genotypes.
rs1229984 and rs671 are common and functionally important genetic variants in the Taiwanese population. Our findings provide strong evidence of additive and synergic risks of ADH1B and ALDH2 variants for alcohol-related disorders and cancer. The results suggested that are reduction in alcohol consumption should be advised as a preventive measure for high-risk patients carrying ADH1B rs1229984 C or the ALDH2 rs671 A allele.
ADH1B rs1229984 和 ALDH2 rs671 是东亚人群中特异性高发的功能变异。这些导致酶活性显著变化的变异与酒精相关疾病和癌症高度相关。目前关于这些变异的累加和协同作用的研究很少且结果不一致。本研究旨在评估 ADH1B rs1229984 和 ALDH2 rs671 与酒精相关疾病和癌症风险的关联。
本队列研究纳入了台湾精准医学倡议数据库中的 42665 名参与者，包括 19522 名和 20534 名 ADH1B 和 ALDH2 携带者。采用单变量和多变量逻辑回归分析两种变异与癌症风险之间的关系。
与非携带者相比，ADH1B rs1229984 变异对酒精相关疾病的影响更强，并与酒精相关癌症的风险增加相关。ADH1B rs1229984 的 CC 基因型与喉、咽和鼻腔癌症显著相关[比值比（OR）=1.56，p=0.0009]、胰腺癌（OR=1.66，p=0.018）和食管癌（OR=4.10，p<0.001）。携带 rs1229984 TC/CC 和 rs671 GG 基因型的参与者患食管癌的风险更高（OR=3.02，p<0.001）。携带 rs1229984 TC/CC 和 rs671 GA/AA 基因型的个体患食管癌的风险增加 381%（OR=4.81，p<0.001）。
rs1229984 和 rs671 是台湾人群中常见且具有重要功能的遗传变异。我们的研究结果提供了强有力的证据，表明 ADH1B 和 ALDH2 变异具有累加和协同作用，增加了与酒精相关的疾病和癌症的风险。结果表明，对于携带 ADH1B rs1229984 C 或 ALDH2 rs671 A 等位基因的高危患者，应建议减少饮酒量作为预防措施。
